PFO and attributable risk with RoPE score

                        cryptogenic stroke, CS (n= 3,023)                                           

 

RoPE score          No patients   Prevalence PFO   PFO attributable   

 

0-3                         613               23(19-26)             0                          

4                            511               35(31-39)             38 (25-48)              

5                            516               34 (30-38)            34 (21-45)             

6                            482               47(42-51)             62 (54-68)         

7                            434               54(49-59)             72 (66-76)            

8                            287               67(62-73)             84 (79-87)         

9-10                       180                73(66-79)             88(83-91)         

 

 

                       cryptogenic stroke (CS) with PFO (N=1,324)

                            No CS+PFO    est 2 yr TIA/CVA (Kaplan-Meier) 

 

                                                                                   

0-3                         108                20(12-28)

4                            148                12(6-18)

5                            186                  7 (6-18)

6                            236                  8 (4-12)

7                            263                  6 (2-10)

8                            233                  6 (2-10)

9-10                       150                   2(0-4)

attributable risk PFO based on Bayes' theorem

 

derivation of data used to make RoPE database

RoPE score for PFO

RoPE score for PFO (Risk of Paradoxical Embolus)

Characteristic    Points

No history of
DM                         1
stroke/TIA              1
HTN                       1
nonsmoker             1
cortical infarct        1

Age
18-29                      5
30-39                      4
40-49                      3
50-59                      2
60-69                      1

total score  -- add sum of parts
cut score used in many articles is 7

source Neurology 2013 au Thaler
 

RoPE score, PFO and CS

Thaler DE, Ruthazer R, Weimar C., et al.  Recurrent stroke predictors differ in medically treated patients with pathogenic v. other PFO's.  Neurology 2014; 83: 221-226.

 

The RoPE score, "Risk of Paradoxical Embolism" score estimates the probability that a PFO discovered in a cryptogenic stroke (CS) patient is incidental or pathogenic, based on Bayes theorem.  Patients with high RoPE score (younger, no vascular risk factors, and a superficial infarct) are more likely to have pathogenic PFO's while patients with low RoPE scores (older, vascular risk factors) are probably incidental.  Authors hypothesized that predictors of recurrent stroke should differ among high and low RoPE score patients and PFO characteristics should be les important in low RoPE score individuals. 

 

Risk factors for recurrence with 1-2.2 yrs of followup  included LOW RoPE scores (one year followup, 7 v. 4 %; two year followup 10 v. 5 %) with 4/5 recurrences being in low score subgroup 

 

Patients with TIA had more recurrent events (HR 1.69) but there was no interaction with RoPE score.

 

Variable associated with risk in low RoPE group include older age, those treated with antiplatelet drugs after initial event.

Variables associated with recurrence in highRoPE score group include history of stroke or TIA, hypermobile interatrial septum, and a small shunt, but not shunt at rest. 

 

Comment of blogger

The article confirms / validates the RoPE score to some extent.  However, the point of closure is to prevent lifetime risk of paradoxical embolus, not 2 year risk.  As such, I am skeptical of the claim that risk of recurrence is lower in high RoPE score group

DJ

MELAS pearls

maternal , mitochondrial dna a3243g

1. Onset before 40
2. Clinical: hemiparesis, hemianopia, cortical blindness; seizures, dementia, migraine, muscle weakness,
3. Associated
Short stature
Hearing loss
Recurrent vomiting
Diabetes
cataracts
developmental delay , cognitive delay AFTER infancy
4. May be relapsing remitting
5. High lactic/abn muscle biopsy
6. AVOID statins and Depakote


MRI parietal-occipital, parietal temporal acute strokes
MRS lactate peak
CSF increased lactate, pyruvate and amino acids
depletes NAD+, NADH+
increases anaerobic metabolism
increases lactic acidosis

progressive strokes and vision loss before age 40
presents in childhood
dx muscle biopsy ragged red fibers on Gomori stain

Rx CoQ
carnitine
L-Arginine
B vitamins
AED's but not depakote

HERNS (RVCL)

Retinal vasculopathy with cerebral leukodystrophy aka cerebroretinal vasculopathy sysndrome aka hereditary endotheliopathy, retinopathy, nephropathy and stroke.

Features
Vision and memory loss
Seizures
Hemiparesis
Apraxia
Dysarthria
dysautonomia
AUT DOM

Onset in fourth decade
Death in five to ten years

Retinopathy is neovascularization of disc, retinal hemorrhage and macular edema.

Half patients have tumor like lesion with cortical sparing resembling malignancy.

Small white matter lesions may resemble MS

Caused by mutations of TREX1 genE
Inherited as aut dome frame shift mutation that encodes dna exonuclease

Retinopathy may respond to bevacizumab

CARASIL pearls

1.  Onset decades 3 to 5

2.  Premature alopecia occurs in teen years

3.  Cervical and lumbar spondylitis occurs in 2d and 3d decades

4.  Mutations in A serine peptides 1 on chromosome 10 q is implicated

Cadasil pearls

1. Strokes are subcortical many with classic lacunae syndromes

2. False negative genetic tests should prompt skin biopsy for granular osmiophic material in the vascular basal lsmina which is a specific finding

3. MRI finding occur in anterior temporal poles (o'Sullivan sign seen in 90 percent) but also extreme capsule and corpus callosum also are distinctive

4.  Other MRI findings are microbleeds and brain atrophy

5.  80 plus NOTCH3 mutations are identified

6.  Migraine with aura occurs in 30 percent, often in 3rd decade long before strokes

Unruptured aneurysm pearls

1. High risk patients who require screening are those with at least two first degree relatives with aneurysm or autosomal dominant polycystic kidney disease

2. Risk factors include age, female gender, family history

3. Risk of rupture in positive family history patients is 17 x higher than in predicted based on size and location in observational studies (Familial Intracranial Aneurysm study).

4. Associated diseases are Marfan syndrome, Ehler Danlos syndrome type IV, aortic coarctation, FMD, and autosomal dominant PCK (12.4 percent). Patients with PCK have increased risk of aneurysm, but their first degree relatives only have 9 percent risk

5. Modifiable risk factors for aneurysm growth include smoking, alcohol abuse and hypertension

6. MCA bifurcation aneurysms are more readily accessible to surgery.

Pearls pediatric stroke

1. Stroke may present with seizures in newborns and even older kids

2. Paroxysmal or stuttering episodes ppt by HV is typical for Moyà Moyà

3. In newborn, consider maternal factors (HTN, DM), perinatal factors, neonatal factors (congenital heart disease, dehydration, infection), and PLACENTAL vasculopathy

4. ACCP recommends against the use of alteplace in pediatric stroke outside clinical trials

5. In Toronto, UFH is used for AIS regardless of mechanism

6. The syndrome of transient cerebral arteriopathy of childhood is a well defined unilateral focal arteriopathy presumably of inflammatory origin. Features include irregular stenosis at carotid T junction. Varicella angiopathy is similar and borrelia and bartonella are also reported. Treatment may include antithrombotics, high dose pulse steroids with long taper, and acyclovir. differential includes Moyà Moyà and dissection of the carotid.

Hypercoagulable misc

1. Homocystinuria, anti phospholipid syndrome, and thrombin deficiency are some of the only syndromes associated with arterial thrombosis

2. The most common acquired thrombophilia is the apl syndrome

3. Seven percent of the white population carries the prothrombin gene mutation but it's rare in black and Asian populations

4. Inherited protein S deficiency autosomal dominant and heterozygous; homozygous is incompatible with life.

5. Protein C deficiency can be due to meningococcemia, liver disease, DIC, ARDS, methotrexate, 5FU, and cyclophosphamide.

Pearls on factor V (Leiden) mutation

1. By far the most common genetic risk factor for thrombophilia

2. Mechanism: increases thrombin production

3. Prevalence varies widely by ethnicity: 5.3 percent in whites, 2.2 percent in Hispanics, 1.3 percent in native Americans, 1.2 percent in African Americans, 0.5 percent in Asian Americans.

4. Five to ten percent of heterozygous carriers in their lifetimes; a sevenfold risk over non carriers but homozygous have an 80 fold risk.

5. 90 to 95 percent of patients with protein C resistance have a point mutation of factor V506Q.

6. Other causes of increased protein C resistance include smoking, oral contraceptives, pregnancy, HRT use, cancer, and anti phospholipid syndrome

7. Syndrome is convincingly linked to venous but not arterial thrombotic events

8. Testing in nonwhite populations is low yield

9. Testing in ischemic stroke in absence of a right to left shunt is low yield

10. In presence of a right to left shunt screening for Dvt with leg ultrasound and pelvic venography is useful

thrombolysis and aneurysms

Post-Thrombolysis Hemorrhage Risk of Unruptured Intracranial Aneurysms; Chen F, Yan S, Jin X, Lin C, Cao J; European Neurology 73 (1-2), 37-43 (Nov 2014)

 

Background/Aims: It has been questioned whether patients with unruptured intracranial aneurysms (IAs) are at a greater risk for the development of intracerebral hemorrhage (ICH) following thrombolytic therapy. We thus performed a meta-analysis to better quantify the risk of post-thrombolysis ICH in patients with acute ischemic stroke and incidental IAs. Methods: We searched PubMed, Web of Science and EMBASE for studies assessing ICH risk in patients with acute ischemic stroke treated with thrombolysis, in relation to the presence of pretreatment IAs. A fixed-effects model meta-analysis was performed. Results: We identified four studies totaling 707 participants receiving intravenous thrombolysis. The prevalence of unruptured IAs was 6.8%. Pooled analysis demonstrates relative risk (RR) for the presence of unruptured IAs and the development of any ICH to be 1.204 (95% CI 0.709-2.043; p = 0.492; I(2) = 0.0%). The RR for sICH is 1.645 (95% CI 0.453-5.970; p = 0.449; I(2) = 28.1%). Conclusion: Intravenous thrombolysis was safe among patients with acute ischemic stroke and incidental unruptured IAs. Future prospective studies with much larger sample sizes are required to clarify the significance of the association between pre-existing unruptured IAs and the development of post-thrombolysis ICH. © 2014 S. Karger AG, Basel.

11

Subarachnoid hemorhage and growth hormone treatment in childhood

Poidvin A, et al.  GH treatment for childhood short stature and risk of stroke in early adulthood. Neurology; 2013; 83: 780-6.

 

6874 children with idiopathic GH deficiency or short stature who stated GH treatment had  rate of hemorrhage from 3.5 to 7.0 compared registry rates. from 1985-96 

 

Editorial (Ichord R) outlines ramifications on screening adults exposed to GH and counselling kids considering GH about risks, which are small but not negligible.

 

 

 

 

Small strokes causing severe vertigo. Frequency of false negative MRI's and

nonlacunar mechanisms.

 

Tehrani ASS, Kattah JC, Mantokoudis G, et al. Neurololgy 2014; 83: 169=173

 

Introduction

Out of acute vestibular syndrome (AVS)  25 % have stroke

80 % of patients with stroke have isolated dizziness/vertigo and 20 % have focal neurologic signs

35 % of strokes are missed, often with negative MRI's. 

 

Results

Out of 190 high risk  AVS presentations, 105 strokes

15  "small strokes" who underwent repeat imaging and found lesion < 10 mm in axial diameter

 

Location of stroke: lateral medulla (60 %)

Etiology Many dissections of vertebral artery, less commonly small vessel, cardiac embolus 

 

"HINTS PLUS" with the plus being a "hearing battery" bedside finger rub picks up the AICA strokes more accurately than MRI

 

My comment-

Lateral medullary infarctions have expected neurologic signs and symptoms that may be missed by physicians who do not know what to look for.  These include decreased gag/phonation, and crossed sensory symptoms (loss of st tract on one foot, dorsal column function on the other) that will pick up many or most of those. I would guess that in AVS with HINTS plus hearing eval plus careful gag/sensory exam some if not most of the strokes could be diagnosed clinically and localized accurately.  MRI is a poor test in this disease, but diagnosis is possible.

 

DJ

Blood pressure variability after thrombolysis: prognostic signficance

Delgado-Mederos E, Ribo M, Rovira A, et al.  Prognostic significance of blood pressure variability after thrombolysis in acute stroke.  Neurology 2008; 71: 552=558.

 

80 stroke patients were prospectively studies who had MCA occlusion treated with t-pa.Multiple BP measurements were obtained.  Recanalization was assessed with TCD at six hours.  NIHSS was done at baseline and 24 hours, MRS at 3 months. 

 

55 % were recanalized.  Both SBP and DBP variability were highly associated with DWI growth (done before and 36 hours after thrombolysis) and outcome, but only in patients who failed to recanalize

 

Notes-- There was a significant decline in overall SBP and DBP in recanalized but not unrecanalized patients. However BP variability was the only factor corresponding to DWI growth.  Authors speculate that treating the swings is as important as treating the outlying numbers.

 

Blogger comment-- this observational study is interesting but not powerful enough to be determinant 

Infarction in the anterior choroidal artery territory: clinical progression and prognosis factors

Chausson N, et al.  JSCD; 2014; 23:8: 2012-7.

 

Authors describe the phenotypes of  anterior choroidal stroke in heretofore unappreciated ways.  They prospectively enrolled patients with AChA disease

 

*One hundred patients were found out of 1234 total (8.1 %) who had AChA strokes

 

*  Main risk factors found were hypertension and (79 %) and diabetes (31 %). 

 

*  88 % had "lacunar" (motor syndrome in 51, sensorimotor in 23, ataxic hemiparesis in 14, isolated ataxia in 4, other 7)

*  only four patients had hemianopia

*  cardioembolic and atherothrombotic causes wee rare

*  3 % mortality but 26 % poor outcomes, invariably due to residual motor deficit and/or spasticity

* Progressive strokes were seen in 46, and 16 with fluctuations, wiht progressions over a mean of 56 hours and being almost exclusively motor

* Use of iv tpa did nto help prevent progression (tpa was used in 12/46 progressors and 9/54 nonprogressors)

* predictor of poor outcome was those who reached an NIHSS of 6 or greater, clinical progression, and infarct size > 15 mm

* Progression was nearly always due to infarct expansion on DWI

* Authors suggest new treatments are needed for this disease.

 

 

Recurrence in Intracranial atherosclerotic disease (ICAD): a stenosis based analysis

Gouvela a, et al.  JSCD, 2014: 23:8:2080-4.

Authors confirmed prior work showing extremely high recurrence rate of stroke in this type of disease:  12.3 per 100 patient years, with mean time to recurrence being 1.7 months among symptomatic intracranial stenosis (SIS) and 0.88 per 100 patient years among asymptomatic intracranial stenosis (AIS). 

They investigated 1302 patients retrospectively, with 218 strokes in 158 patients, of which 77 were symptomatic and 141 asymptomatic.  Patients with AIS were older, had more AF

blogger note-- interesting article that splits ICAD ina new way, to AIS and SIS that has very different clinical outcomes.

Odds ratio and population attributable risk of 10 factors estimated to acount for 90 % of ischemic stroke risk

Risk factor            OR              PAR    (confidence intervals available elsewhere)

 

hypertension          2.64            34.6

current smoking     2.09            18.9

waist to hip ratio    1.65             26.5

Diet risk score       1.35             18.8

Regular exercise    0.69             28.5

Diabetes mellitus   1.36             5.0

ETOH (> 30/mo)     1.51             3.8

Stress/depression   1.30            4.6

Cardiac causes       2.38            6.7

ratio apo B/A1        1.89             24.9

 

Notes

Spouses of smokers have double risk of stroke.  Much benefit of cessation occurs in first 6 months.  Cessation leads to return to baseline risk within five years.

 

Fives risk factors  related to lifestyle and risk

1. Absent current smoking

2. 30 + minutes per day of exercise

3. healthy diet

4.  moderate ETOh consumption

5.  BMI < 25

If all five risk factors are favorable,   RR is -.2, PAR is -53.

 

Cretan Mediterranean diet is the best one; those randomized to it had 70 % less CV events within 27 months

This diet contains more fat esp olive oil.  Its much lower in meat and dairy products and uses fruit as desert. It has high levels of canola nad olive oil, high fruit/vegetable/lentils/beans and nuts.  Avoid trans fats and egg yolks; meat every other day.

 

Ottawa Model of Smoking Cessation

systematic

Identify smoking status-- have you used any form of tobacco in the past six months? The past seven days?

Document-- smoking history (pack years); previous quit attempts, time to first cigarette

Advise--- "There is nothing more important that cessation. We can help you with that"

Pharmacotherapy-- readily available medicine, prescribed appropriately

Followup-- FP; telephone calls; community resources.

ACC/AHA Guisdelines for postcardiac surgery atrial fibrillation; and CABG in general

* patients with pre-existing AF receiving antiarrhythmics or rate controlling agents should be continued ont hese in postop period.

 

*  Oral beta blocker is recommended to prevent post op AF in patients undergoing cardiac surgery-- unless contraindicated

 

*  An AV nodal blocking agent is recommended for postop rate control in patients who develop postop AF

 

* Preop amiodarone decreases the incidence of AF in patients undergoing cardiac surgery  and represents appropriate prophylactic therapy for patients at high risk of AF

 

*  Its reasonable to restore sinus rhythm pharmacologically or through cardioversion among patients who develop postoperative AF

 

*  It is reasonable to administer anti-arrhytmics to maintain SR in patients with postop refractory or recurrent AF

*  Antithrombotic medication is reasonable to administer in patients who develop postop AF

 

*  Prophylactic sotalol may be considered in high risk patients. 

 

Additional points for cardiac surgery-- evidence based

 

*Matching preop and postop BP may reduce the risk of perioperative stroke or death  III/B

 

* Preop statins reduce the perioperative stroke risk in cardiac surgery  IB/A

 

*  Antiplatelet therapy eg ASA reduces the postop stroke risk without increasing the risk of bleeding complications  Ia/A

 

*  Discontinuing warfarin or antiplatelet agents in anticipation of surgery increases the risk of perioperative stroke, with the highest risk in patients with CAD

Benefit of CEA in different conditions

Degree of stensois         Studies        Recc           Risk reduction

 

Symptomatic stenosis

   70-99%                       NASCET     CEA LEVEL A       16.5 % at two years

   >60 %                         ECST               "                     11.6 % at 3 years

   50-69 %                       NASCET           "                    10.1 % at 5 years

 

 

Asymptomatic stenosis

 

>60 %                            ACAS, ACST     "                     6.3 % at five years

RISK OF HEMORRHAGE

 

-- some literature favors early surgery for patients without early ICH on CT scans

 

-- of those who hemorrhaged, hemorhhage occured 3-6 days after surgery when patients were improving or ambulatory.  They occurred in 6/900 patients studied

 

-- Dosick et al. reported 9.5 % restroke incidence with six week waiting period before CEA

 

--In NASCET 4.9 % of 103 patients  (5 patients) had restroke within 30 days of trial entry if treated medically

 

-- In a variety of studies patients operated within 3 weeks had 3 % stroke risk, those operated beyong 3 weeks had a 5.3 % stroke risk

 

 

 

 

Timing of tpa; outcomes

0-90 minites  odds ratio for favorable outcome at 3 months based on 4 point decline of NIHSS is 2.11

90-180 minutes-- odds ratio is 1.69

 

In NINDS trials, poor outcomes as defined by MRS >3 at 24 hours were predicted by NIHSS>22

OR

NIHSS>17 plus AF

Duration of dual antiplatelet therapy after implantation of drug eluting stents

Park et al. NEJM 2010; 362: 1374-82. 
Conclusion
use of dual antiplatelet therapy more than 12 months among patients who received drug eluting stents was not significantly more effective than aspirin monotherapy. 

Lenient v. strict rate control in patients with atrial fibrillation

Gelder et al.  NEJM 2010; 362: 1363-73

study of 614 patients showed that among patients with permanent AF, lenient rate control is as effective as strict rate control and is easier to achieve.

vitatops study

http://ac.els-cdn.com/S1474442210701873/1-s2.0-S1474442210701873-main.pdf?_tid=c39f01f0-f232-11e3-9c1b-00000aacb361&acdnat=1402578739_e5b1b16c09ddc46f739cdc8e3ecf08fb

 

b vitamins and folic acid was safe but not more effective than placebo to prevent strokes

Fingolimod and atrial fibrillation

Rolf et al.  Paroxysmal atrial fibrillation after initiation of fingolimod for multiple sclerosis treatment

 

42 year old male had PAF on initiation, resolution on withdrawal of, recurrence on reinitiation and reresolution permanently on discontinuation of fingolimod.  Extensive cardiac testing was negative.   This is different than the bradycardia that is known to occur with fingolimod which requires initiation with cardiac monitoring. 

 

Authors note that fingolimod is an agonist of S1P-R1,2,3 in cardiovascuklar system.  In atrial myocytes, binding of the receptors causes activation of the potassium channels leading to an inward K current and decreased firing rate.  Therefore drug causes bradycardia or AV conduction blockade.  There is in animal models, S1P induced reperfusion tachyarrythmias. 

IV thrombolysis and renal disease

Neurology 2013; 81: 1780-8.

Studied 4780 ivt treated patients, of whom 25.5 % had a low GFR below 60 mL/min.  Low GFR was significantly associated with poor 3 month outcome  death and sICH; lower GFR "might be a better risk indicator than age" and a decrease by 10 mL/min/1.73 m@ has a similar impact on death or SIC as one point on the NIHSS

IV tpa is safe in Chagas disease related strokes

Neurology 2013;81:1773-5.  Out of a series of 240 patients in Brazil, 24 (13.8%) had positive serologic testing for Chagas disease.  They more likely had heart failure and higher NIHSS but did NOT have more symptomatic intracranial hemorrhage or in hospital death than patients without.  Conclusion:  Chagas disease diagnosis does not preclude use of tpa.
editor note: does not apply to those with known Chagas disease vasculitis, and a small number was studied, and positive serology is different than having severe disease

AHA guidelines for stroke prevention in women

http://stroke.ahajournals.org/content/early/2014/02/06/01.str.0000442009.06663.48

Syndrome of the trephined

Skin "sinks" weeks to months after a craniectomy.  It can have minor or major presentations, rarely coma, and be relieved with placing patient in trendelenberg position and using a titanium mesh.  

Abcd2

Abcd2 and stroke risk

Cardiac papillary fibroelastoma: A comprehensive

 

Cardiac papillary fibroelastoma: A comprehensive

analysis of 725 cases

Ramesh M. Gowda, MD,a Ijaz A. Khan, MD, FACP, FACC,b Chandra K. Nair, MD, FACP, FACC,b

Nirav J. Mehta, MD,b Balendu C. Vasavada, MD, FACC,a and Terrence J. Sacchi, MD, FACCa Omaha, Neb, and

Brooklyn, NY

 

(Am Heart J 2003;146:404–10.)

 

Seven hundred twenty-five cases of CPF were identified. Males comprised 55% of

patients. Highest prevalence was in the 8th decade of life. The valvular surface was the predominant locations of tumor.

The most commonly involved valve was the aortic valve, followed by the mitral valve. The left ventricle was the predominant

nonvalvular site involved. No clear risk factor for development of CPF has been reported. Size of the tumor varied

from 2 mm to 70 mm. Clinically, CPFs have presented with transient ischemic attack, stroke, myocardial infarction, sudden

death, heart failure, presyncope, syncope, pulmonary embolism, blindness, and peripheral embolism. Tumor mobility

was the only independent predictor of CPF-related death or nonfatal embolization. Symptomatic patients should be

treated surgically because the successful complete resection of CPF is curative and the long-term postoperative prognosis

is excellent. The symptomatic patients who are not surgical candidates could be offered long-term oral anticoagulation,

although no randomized controlled data are available on its efficacy. Asymptomatic patients could be treated surgically if

the tumor is mobile, as the tumor mobility is the independent predictor of death or nonfatal embolization. Asymptomatic

patients with nonmobile CPF could be followed-up closely with periodic clinical evaluation and echocardiography, and

receive surgical intervention when symptoms develop or the tumor becomes mobile.

 

Additional pearls from this review:

 

1. 

Cardiac

papillary fibroelastomas (CPF), the second most

common primary cardiac tumors, are benign endocardial

papillomas predominantly affecting the cardiac

valves, and account for three fourths of all cardiac valvular

tumors. They consist of a small, highly papillary,

pedunculated and avascular tumor, covered by a single

layer of endothelium, containing variable amounts of

fine elastic fibrils arranged in whorls in a hyaline

stroma.

2.

Although CPF are rare and histologically benign

tumors, they may result in life-threatening complications,

such as stroke, acute valve dysfunction, embolism,

and sudden death.

3.

The most common clinical presentation was of transient

ischemic attack or stroke (n 120 patients). The

other manifestations were angina (n 49 patients),

myocardial infarction (n 28 patients), sudden death

(n 21 patients), heart failure (n 24 patients), presyncope

or syncope (n 12 patients), pulmonary

embolism (n 3 patients), blindness (n 7 patients),

mesenteric ischemia (n 2 patients), peripheral emboli

(n 3 patients), and renal infarction (n 1 patient).

In patients with mitral valve tumors, stroke was

the most common clinical presentation, but in patients

with aortic valve tumors, sudden death and myocardial

infarction were the 2 most common presentations. In

a large number of patients, tumors were identified as

incidental findings at autopsy (n 209 patients) or at

surgery for other cardiac reasons (n 9 patients).

4.

The major immunophenotypic

difference between CPF and cardiac myxoma was the

frequent presence of muscle-specific actin in the stellate

cells of the stroma in cardiac myxoma but not in

CPF.

5. 

Because most CPF are located in the left heart (95%),

systemic embolism in particular is frequent. In a majority

of CPF cases with embolism, the cerebral arteries,

including retinal arteries, are affected, and transient

ischemic attack, stroke, and sudden visual loss have

been reported

6.

The classic

diastolic tumor plop, which is heard in one third of

patients with atrial myxoma, has not been described

with CPF, except in 1 case where a tricuspid valve

CPF was associated with a tumor plop.46

7. Diferential diagnostic analysis:

Cardiac myxoma

is a predominant left atrial tumor, and is usually attached

to the atrial septum by a stalk. Histologically,

myxoma differs from CPF by presence of polygonal

 

myxoma cells and blood vessels within papillae.125

The papillae of CPF are devoid of blood vessels. Calretinin

staining may be a useful way to distinguish between

myxoma and CPF.218 Cardiac fibroma, which is

a separate entity, frequently demonstrates calcification

and cystic degeneration. Cardiac rhabdomyomas are

predominant myocardial neoplasms seen in infants and

children.214 Metastatic tumors of the heart are more

frequent than the primary tumors.1 Unlike CPF, malignant

tumors commonly involve the pericardium and

myocardium, and are usually accompanied by systemic

symptoms. However, with both primary and metastatic

tumors, the clinical course may be complicated by emboli.

Ljevak J, Mismas A, Bazina A, et al.
An infrequent type of stroke with an unusual cause and successful therapy: basilar artery occlusion caused by a cardiac papillary fibroelastoma recanalized 12 hours after onset [In Process Citation]
Intern Med (Japan), 2013, 52(2) p277-9

 

take home points: Again, BA can be recanalized later than other vessels; this tumor type is very sensitive to lysis

Etiology and treatment of ischaemic stroke in patients with (sup)-thalassemia major.

Eur J Neurol 2011 Dec;18(12):1426-8    (ISSN: 1468-1331)

 

BACKGROUND AND PURPOSE: Although hypercoagulability-induced thromboembolism is generally accepted as cause of cerebral ischaemia in thalassemic patients, cardiogenic embolism has been recently suggested as another possible stroke etiology. METHODS: We present four adult (sup)-thalassemia major patients with manifest cardiac involvement who suffered territorial strokes. RESULTS: In the presence of siderotoxic cardiomyopathy and arrhythmia, we assumed cardiogenic embolism as etiology of stroke and initiated oral anticoagulation as preventive medication. Two of our patients were the first (sup)-thalassemia major patients who underwent successful thrombolysis with rtPA. CONCLUSIONS: Cardioembolism seems to be the cause of stroke in cases of (sup)-thalassemia major. Thrombolysis can be applied in the setting of acute brain ischaemia in such high risk patients. [ 2011 The Author(s). European Journal of Neurology 2011 EFNS.].

 

Comment:  Take home points

1.  Thal cases can be cardioembolic not just hypercoagulable and may benefit from anticoagulation

2.  Thrombolysis might help in some cases

anticoagulation in acute stroke

Lancet Neurology 2013 published a metaanalysis of studies showing no benefit of anticoagulation in acute stroke.  However, like Freddy Krueger, the debate will not die.  Below is an excerpt from the editorial by Hart et al.  that lays out some of the remaining points of contention.

A meta-analysis of 24 trials involving 23 748 patients with acute stroke found that early anticoagulation compared with no anticoagulation reduced recurrent ischaemic stroke and venous thromboembolism at the cost of increased intracranial and extracranial haemorrhage, with no overall reduction in death or disability.² Consequently, guidelines for stroke management now recommend that anticoagulants should not be used for the management of acute stroke caused by common cerebrovascular disorders (including atrial fibrillation).³ Nonetheless, the question remains: are there acute stroke patients at high risk of thrombotic events and low risk of bleeding who might yet benefit from early anticoagulant therapy?

In this issue of The Lancet Neurology, William Whiteley and colleagues⁴ report the results of a pooled individual patient-level analysis of the five largest randomised trials that have tested heparins in patients with acute ischaemic stroke. The authors developed risk prediction models to identify acute stroke patients The analyses by Whiteley and colleagues provide no support for the use of anticoagulants in the management of patients with acute stroke, but the results must be interpreted with caution. First, despite careful efforts by the investigators to derive the best risk-prediction models, they were only modestly predictive of thromboembolic and bleeding events (C-statistics in the order of 0·6), thereby reducing the quality of the evidence and limiting the strength of the conclusions. Second, the conclusion must necessarily be restricted to the subgroups common to the trial databases; for example, the presence of large artery atherosclerosis was not considered.⁵ Third, uncertainty remains regarding the role of heparins in patients with uncommon conditions resulting in acute brain ischaemia. These include patients with acute cerebral venous thrombosis, small-to-moderate brain infarcts due to cerebral arterial dissection, aseptic embolism from prosthetic cardiac valves, mobile left ventricular thrombi, and aortic arch plaque with protruding overlying thrombi.

The balance between risks and benefits of heparins also remains unclear for patients with acute transient ischaemic attack or minor ischaemic strokes who were poorly represented in the randomised trials. These patients have a low risk of secondary haemorrhagic transformation because they do not have substantial areas of acute brain necrosis. A randomised trial that assessed the combination of clopidogrel plus aspirin in patients with acute transient ischaemic attack found a benefit of the intensive antiplatelet therapy,⁶ and other trials testing dual antiplatelet therapy in patients with acute ischaemic attack or minor ischaemic stroke are ongoing.⁷ Whether early anticoagulation provides benefit for these patients needs to be assessed.

Recently introduced novel oral anticoagulants that selectively target thrombin (dabigatran etexilate) or factor Xa (rivaroxaban, apixaban) are attractive candidates for acute stroke treatment because they work rapidly (within 2–3 h) after oral administration. The most important advantage of the novel oral anticoagulants over warfarin is the sharply decreased risk of intracerebral haemorrhage seen during long-term treatment in patients with atrial fibrillation.⁸ If the novel oral agents are associated with a similarly low risk of secondary brain haemorrhage after acute stroke, the balance between risks and benefits of early anticoagulation might be altered in favour of treatment, making this a priority for future research.

Despite multiple randomised trials testing heparins in patients with acute ischaemic stroke, and also the rigorous efforts by Whiteley and colleagues to identify subsets of patients defined by thromboembolic and bleeding risk that might benefit from early anticoagulation, the value of this approach has not been established for any patient group.⁴ However, promising early data with the use of combined antiplatelet therapy and the emergence of novel oral anticoagulants with a rapid onset of action and low risk of intracranial haemorrhage means that anticoagulant therapies for patients with acute brain ischaemia remains a fruitful area for future clinical research.

Hemorrhagic transformation in patients with acute ischaemic stroke and an indica

Hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation; Marsh EB, Llinas RH, Hillis AE, Gottesman RF; European Journal of Neurology (Mar 2013)

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) can occur in patients following acute ischaemic stroke in the form of hemorrhagic transformation, and results in significant long-term morbidity and mortality. Anticoagulation theoretically increases risk. We evaluated stroke patients with an indication for anticoagulation to determine the factors associated with hemorrhagic transformation. METHODS: Three-hundred and forty-five patients with ICD-9 codes indicating: (i) acute ischaemic stroke; and (ii) an indication for anticoagulation were screened. One-hundred and twenty-three met inclusion criteria. Data were collected retrospectively. Neuroimaging was reviewed for infarct volume and evidence of ICH. Hemorrhages were classified as: hemorrhagic conversion (petechiae) versus intracerebral hematoma (a space occupying lesion); symptomatic versus asymptomatic. Using multivariable logistic regression, we determined the hypothesized factors associated with intracerebral bleeding. RESULTS: Age [odds ratio (OR) = 1.50 per 10-year increment, 95% confidence interval (CI) 1.07-2.08], infarct volume (OR = 1.10 per 10 ccs, 95% CI 1.06-1.18) and worsening category of renal impairment by estimated glomerular filtration rate (eGFR; OR = 1.95, 95% CI 1.04-3.66) were predictors of hemorrhagic transformation. Ninety- nine out of 123 patients were anticoagulated. Hemorrhage rates of patients on and off anticoagulation did not differ (25.3% vs. 20.8%; P = 0.79); however, all intracerebral hematomas (n = 7) and symptomatic bleeds (n = 8) occurred in the anticoagulated group. CONCLUSIONS: The risk of hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation is multifactorial, and most closely associated with an individual's age, infarct volume and eGFR.

MR Rescue NEJM 2013

Background
Whether brain imaging can identify patients who are most likely to benefit from
therapies for acute ischemic stroke and whether endovascular thrombectomy improves
clinical outcomes in such patients remains unclear.
Methods
In this study, we randomly assigned patients within 8 hours after the onset of largevessel,
anterior-circulation strokes to undergo mechanical embolectomy (Merci
Retriever or Penumbra System) or receive standard care. All patients underwent
pretreatment computed tomography or magnetic resonance imaging of the brain.
Randomization was stratified according to whether the patient had a favorable
penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral
pattern (large core or small or absent penumbra). We assessed outcomes
using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead).
Results
Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment
was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization
in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality
was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate
differed across groups. Among all patients, mean scores on the modified Rankin
scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P = 0.99).
Embolectomy was not superior to standard care in patients with either a favorable
penumbral pattern (mean score, 3.9 vs. 3.4; P = 0.23) or a nonpenumbral pattern
(mean score, 4.0 vs. 4.4; P = 0.32). In the primary analysis of scores on the 90-day
modified Rankin scale, there was no interaction between the pretreatment imaging
pattern and treatment assignment (P = 0.14).
Conclusions
A favorable penumbral pattern on neuroimaging did not identify patients who would
differentially benefit from endovascular therapy for acute ischemic stroke, nor was
embolectomy shown to be superior to standard care. (Funded by the National Institute
of Neurological Disorders

 

Blogger comment:  key point here is mean time to vascularization has to be less than 8 hours.  MR rescue should be done within six or preferably four hours.

IMS 3 article

Endovascular Therapy after Intravenous
t-PA versus t-PA Alone for Stroke
Joseph P. Broderick, M.D., Yuko Y. Palesch, Ph.D., Andrew M. Demchuk, M.D., et al NEJM 2013

 

BACKGROUND
Endovascular therapy is increasingly used after the administration of intravenous tissue
plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic
stroke, but whether a combined approach is more effective than intravenous t-PA
alone is uncertain.
METHODS
We randomly assigned eligible patients who had received intravenous t-PA within
3 hours after symptom onset to receive additional endovascular therapy or intravenous
t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified
Rankin scale score of 2 or less (indicating functional independence) at 90 days
(scores range from 0 to 6, with higher scores indicating greater disability).
RESULTS
The study was stopped early because of futility after 656 participants had undergone
randomization (434 patients to endovascular therapy and 222 to intravenous t-PA
alone). The proportion of participants with a modified Rankin score of 2 or less at
90 days did not differ significantly according to treatment (40.8% with endovascular
therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage
points; 95% confidence interval [CI], −6.1 to 9.1, with adjustment for the National
Institutes of Health Stroke Scale [NIHSS] score [8–19, indicating moderately severe
stroke, or ≥20, indicating severe stroke]), nor were there significant differences for
the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8
percentage points; 95% CI, −4.4 to 18.1) and those with a score of 19 or lower (−1.0
percentage point; 95% CI, −10.8 to 8.8). Findings in the endovascular-therapy and
intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively;
P = 0.52) and the proportion of patients with symptomatic intracerebral hemorrhage
within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P = 0.83).
CONCLUSIONS
The trial showed similar safety outcomes and no significant difference in functional
independence with endovascular therapy after intravenous t-PA, as compared with
intravenous t-PA alone. (Funded by the National Institutes of Health and others;
ClinicalTrials.gov number, NCT00359424.)

 

Blogger comment

 

There's a lot of issues with the studies:

IMS III:

1) IMS III only included patients that arrived in <3 hours and could get IV tPA.

2) Patients that are not candidates for IV tPA (recent surgery, coumadin, etc) undergo endovascular mechanical thrombectomy.

3) 5197 patients were screened for IMS III, but only 656 patients randomized, which typically means the confined scope of a PRCT does not generalize to the real world.

4) For most of IMS III, noncontrast CT was the only imaging (CTA was only added later) which means there were likely a significant number of patients withOUT an occlusion that were randomized in the study (in the Ciccone study, 10% of patients did not have an occlusion!).

5) IMS III included a hodge-podge of endovascular treatments including EKOS, which no one uses, and IA tPA, which is rarely used now that we have mechanical thrombectomy devices.

6) The study was halted because of futility, thus the number of patients studied was not enough for the study to be adequately powered to demonstrate a difference.

7) IMS III was a comparison of IV tPA versus IV tPA plus endovascular therapy. What the study shows is maybe IV tPA is our best treatment. However, the way we practice, and most high-volume stroke centers are the same, is we give IV tPA to eligible candidates and only perform endovascular therapy in patients that are not eligible for IV tPA, or who receive IV tPA and the IV tPA does not work.

8)  Current devices in past year are much more effective and current protocols stress earlier door to needle.

Synthesis trial

SYNTHESIS N Engl J Med 2013

Background
In patients with ischemic stroke, endovascular treatment results in a higher rate of
recanalization of the affected cerebral artery than systemic intravenous thrombolytic
therapy. However, comparison of the clinical efficacy of the two approaches is
needed.
Methods
We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours
after onset, to endovascular therapy (intraarterial thrombolysis with recombinant
tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a
combination of these approaches) or intravenous t-PA. Treatments were to be given
as soon as possible after randomization. The primary outcome was survival free of
disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with
0 indicating no symptoms, 1 no clinically significant disability despite symptoms,
and 6 death) at 3 months.
Results
A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous
t-PA. The median time from stroke onset to the start of treatment was
3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001).
At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the
intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for
age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence
interval, 0.44 to 1.14; P = 0.16). Fatal or nonfatal symptomatic intracranial
hemorrhage within 7 days occurred in 6% of the patients in each group, and there
were no significant differences between groups in the rates of other serious adverse
events or the case fatality rate.
Conclusions
The results of this trial in patients with acute ischemic stroke indicate that endovascular
therapy is not superior to standard treatment with intravenous t-PA. (Funded
by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.)

 

Blogger comment-- endovascular v tpa does not represent real world since current protocol is patients get iv if eligible and both if iv does not work,and endovascular alone if not eligible for iv. Also hodgepodge of old interventional methods were used.

SYNTHESIS (Italian Study):

1) This study only randomized patients that arrived in < 4.5 hours and were eligible candidates for IV tPA. For same reasons as above, this is a very narrow scope of patients.

2) This study was a comparison of IV tPA versus IA tPA (additional devices could be used). IA tPA is rarely used as an endovascular therapy now that we have mechanical devices.

3) No CTA was allowed in this study. Only noncontrast head CT. 10% of patients randomized to IA therapy had no occlusion on angiogram, and these patients because the protocol dictated, were given IA tPA anyways even if they had no occlusion!

4) In his presentation, Ciccone showed that the time-to-treatment was significantly different: >60 minutes longer in the IA treatment arm of the study.

5) It is not clear how many patients were screened to arrive at the final enrollment of 362.

Renal Dysfunction as a Predictor of Stroke and Systemic Embolism in Patients wit

Renal Dysfunction as a Predictor of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation: Validation of the R2CHADS2 Index in the ROCKET AF and ATRIA Study Cohorts; Piccini JP, Stevens SR, Chang Y, Singer DE, Lokhnygina Y, Go AS, Patel MR, Mahaffey KW, Halperin JL, Breithardt G, Hankey GJ, Hacke W, Becker RC, Nessel CC, Fox KA, Califf RM; Circulation (Dec 2012)BACKGROUND: We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial. METHODS AND RESULTS: In ROCKET AF, 14,264 patients with nonvalvular AF and creatinine clearance (CrCl) ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non-central nervous system (CNS) embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA, an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 (4.0%) patients experienced primary endpoint events. Reduced CrCl was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack (TIA). Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, and vascular disease of the heart and limbs (C-index 0.635). A model including CrCl (R(2)CHADS(2)) improved net reclassification index (NRI) by 6.2% when compared with CHA(2)DS(2)VASc (C-statistic=0.578) and 8.2% when compared with CHADS(2) (C-statistic=0.575). The inclusion of estimated glomerular filtration rate<60 and prior stroke or TIA in a model with no other covariates led to a C-statistic of 0.590. Validation of R(2)CHADS(2) in an external, separate population improved NRI by 17.4% (95% CI 12.1-22.5%) relative to CHADS(2). CONCLUSIONS: In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Unique identifier: NCT00403767.

8

FDA: Don't use dabigatran with mechanical valves

ROCKVILLE, Md -- December 20, 2012 -- The US Food and Drug Administration (FDA) is informing healthcare professionals and the public that the anticoagulant dabigatran etexilate mesylate (Pradaxa) should not be used to prevent stroke or blood clots in patients with mechanical prosthetic heart valves.

A clinical trial in Europe (RE-ALIGN) was recently stopped because dabigatran users were more likely to experience strokes, heart attacks, and blood clots forming on the mechanical heart valves than were warfarin users. There was also more bleeding after valve surgery in the dabigatran group versus the warfarin group.

Dabigatran is not approved for patients with atrial fibrillation caused by heart valve problems.

The FDA is requiring a contraindication of dabigatran in patients with mechanical heart valves. Health care professionals should promptly transition any patient with a mechanical heart valve who is taking dabigatran to another medication.

The use of dabigatran in patients with bioprosthetic valves has not been evaluated and cannot be recommended.

Patients with all types of prosthetic heart valve replacements taking dabigatran should talk to their health care professional as soon as possible to determine the most appropriate anticoagulation treatment.

Data Summary
In the RE-ALIGN trial, patients with bileaflet mechanical prosthetic heart valves (recently implanted or implanted more than 3 months prior to enrolment) were randomised to receive warfarin or dabigatran (150, 220, or 300 mg twice-daily). Initial dosing of dabigatran was determined by renal function. In the warfarin group, the target international normalized ratio (INR) was 2 to 3 or 2.5 to 3.5, depending on the presence of risk factors and the position of the mechanical prosthetic heart valve.

The study was terminated early because the dabigatran arm had significantly more thromboembolic events (valve thrombosis, stroke, and myocardial infarction) and major bleeding (predominantly postoperative pericardial effusions requiring intervention for hemodynamic compromise) than did the warfarin arm. These bleeding and thromboembolic events were reported in patients who were initiated on dabigatran postoperatively within 3 days after mechanical bileaflet valve implantation and in patients whose valves had been implanted more than 3 months previously.

Adverse events should be reported to the FDA's MedWatch program:
1-800-332-1088
1-800-FDA-0178 Fax
Report a Serious Problem
MedWatch Online
Download Forms
Regular Mail: Use postage-paid
Mail to: MedWatch 5600 Fishers Lane
Rockville, MD 20857

Atenolol improves outcome in ICH

Is beta-blocker (atenolol) a preferred antihypertensive in acute intracerebral hemorrhage?; Kalita J, Misra UK, Kumar B; Neurological Sciences (Oct 2012)

 

The mortality in intracerebral hemorrhage (ICH) is mainly due to raised intracranial pressure, and its complications mediated by sympathetic overactivity. There is paucity of studies evaluating the role of beta-blockers in the outcome of ICH. This study reports the role of atenolol in reducing mortality, pneumonia, systemic inflammatory response syndrome (SIRS), and 3 months outcome in the patients with hypertensive ICH. 138 consecutive patients with hypertensive ICH were included and their stroke risk factors and clinical details were recorded. Consciousness was assessed by Glasgow Coma Scale and severity of stroke by Canadian Neurological Scale. Volume of hematoma was measures on CT scan and occurrence of SIRS and pneumonia were noted. 3 months outcome was categorized into good (Barthel index>12) and poor (BI < 12). The patients were categorized into those receiving atenolol and nonatenolol. The effects of atenolol on stroke outcome parameters were evaluated. Seventy-nine patients received atenolol and 59 did not and they mainly received amlodipine. There was no difference in the base line clinical characteristics between the two groups except smoking (P = 0.01) and baseline blood pressure (P = 0.007). Atenolol significantly reduced the mortality (11.4 vs 37.3 %, P < 0.0001), SIRS (16.4 vs 40.9 %, P = 0.007), and pneumonia (8.9 vs 30.5 %, P = 0.002) compared to those not receiving atenolol. At 3 months, patients with atenolol had insignificantly better outcome compared to nonatenolol group (49.1 vs 31.9 %, P = 0.11). Use of atenolol in hypertensive ICH results in reduction in mortality, SIRS, and pneumonia which may be due to its β-adrenergic blocking effect.

warfarin v. dabigatran RE-LY trial

Intracranial Hemorrhage in Atrial Fibrillation Patients During Anticoagulation With Warfarin or Dabigatran: The RE-LY Trial; Hart RG, Diener HC, Yang S, Connolly SJ, Wallentin L, Reilly PA, Ezekowitz MD, Yusuf S; Stroke (Apr 2012)

BACKGROUND AND PURPOSE: Intracranial hemorrhage is the most devastating complication of anticoagulation. Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined. METHODS: Analysis of 18 113 participants with atrial fibrillation in the Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) trial assigned to adjusted-dose warfarin (target international normalized ratio, 2-3) or dabigatran (150 mg or 110 mg, both twice daily). RESULTS: During a mean of 2.0 years of follow-up, 154 intracranial hemorrhages occurred in 153 participants: 46% intracerebral (49% mortality), 45% subdural (24% mortality), and 8% subarachnoid (31% mortality). The rates of intracranial hemorrhage were 0.76%, 0.31%, and 0.23% per year among those assigned to warfarin, dabigatran 150 mg, and dabigatran 110 mg, respectively (P<0.001 for either dabigatran dose versus warfarin). Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg (n=13 and n=11, respectively) versus warfarin (n=32; P<0.01 for both). Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran (11 patients with each dose) compared with warfarin (24 patients; P<0.05 for both dabigatran doses versus warfarin). Independent predictors of intracranial hemorrhage were assignment to warfarin (relative risk, 2.9; P<0.001), aspirin use (relative risk, 1.6; P=0.01), age (relative risk, 1.1 per year; P<0.001), and previous stroke/transient ischemic attack (relative risk, 1.8; P=0.001). CONCLUSIONS: The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran. Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin. Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage.

212 Stars

Star

(no subject)

Dose-dependent effect of early antiplatelet therapy in acute ischaemic stroke; Meves SH, Overbeck U, Endres HG, Krogias C, Neubauer H; Thrombosis and Haemostasis 107 (1), (Dec 2011)

Antiplatelet agents are essential in treating patients with acute ischaemic stroke (AIS) to prevent recurrent ischaemic events. The aim of this study was to evaluate the effectiveness of early antiplatelet therapy with different aspirin (ASA) dosages in patients with AIS. This observational study included 454 patients with AIS in whom antiplatelet treatment was initiated. The antiplatelet effect was determined by whole blood aggregometry within 48 hours after antplatelet therapy was initiated. An impedance change exceeding 0 Ω after stimulation with arachidonic acid was defined as ASA low response (ALR) and ≥5 Ω in ADP-stimulated specimen as clopidogrel LR. Of the study group 53.5% patients were treated with 200 mg ASA orally, 27.5% with 500 mg ASA intravenously, 8.6% with 100 mg ASA orally, and 7.7% with 75 mg clopidogrel. A dose-dependent antiplatelet effect of ASA treatment was found: 18.4% of patients with 500 mg ASA intravenously were ALR, in contrast to 32.5% on 200 mg and 35.9% on 100 mg ASA orally. Clopidogrel treatment without a loading dose resulted in a high proportion of LR (45.7%). Using the propensity score method revealed a three times higher risk for ALR for patients treated with ASA 200 mg [odds ratio 2.99 (1.55-5.79)] compared to treatment with ASA 500 mg. In conclusion, initiating antiplatelet therapy in patients with AIS resulted in a dose-dependent insufficient platelet inhibitory effect. Our findings suggest using a loading dose of 500 mg ASA intravenously as this seems to be favourable when a sufficient early platelet inhibitory effect is wanted.

comment- debate over aspirin dose never ends.  However, we treat patients, not lab tests and it would be interesting to know if there were any clinical effects or side effects of high v. low dose aspirin

dual antiplatelet therapy for 7 days in intracranial occlusive disease

The effectiveness of dual antiplatelet treatment in acute ischemic stroke patients with intracranial arterial stenosis: a subgroup analysis of CLAIR study; the CLAIR Study Investigators; International Journal of Stroke (Aug 2012)

BACKGROUND: Dual antiplatelet therapy with clopidogrel and aspirin reduces the presence and number of microembolic signals in patients with large artery disease. However, whether it is effective in patients with intracranial disease alone remains uncertain. We performed a subgroup analysis of the The CLopidogrel plus Aspirin for Infarction Reduction (CLAIR in acute stroke or transient ischemic attack patients with large artery stenosis and microembolic signals) study of only patients with intracranial occlusive disease, excluding those with extra cranial disease. METHODS: CLAIR was a randomized-controlled, open-label, multicenter clinical trial with blinded outcome evaluation, which recruited patients with symptoms of ischemic stroke or transient ischemic attack within seven-days of onset, with large artery stenosis verified by transcranial Doppler and carotid ultrasound, and with microembolic signals detected by transcranial Doppler recording. All patients were randomized to receive clopidogrel plus aspirin daily for seven-days (dual treatment), or aspirin alone for seven-days (monotherapy). Repeated transcranial Doppler recordings for microembolic signals were made on day one, two, and seven. This subgroup study only analyzed the patients with purely intracranial large artery disease and excluded those with extra cranial stenosis. RESULTS: There were 70 patients recruited with purely intracranial stenosis, 34 in the dual treatment group and 36 in the monotherapy group. The proportion of the patients with positive emboli at day seven in the dual treatment group was significantly lower than that in the monotherapy group (relative risk reduction 56·5%, 95% confidence interval 2·5-80·6; P = 0·029). The number of emboli in the dual treatment group decreased significantly at day two (P = 0·043) and day seven (P = 0·018) compared with the monotherapy group. After adjustment for the number of emboli at day one, the effect of dual treatment was still significant for the reduction of presence (relative risk reduction 56·0%; 95% confidence interval 5·4-79·6; P = 0·036) and number (adjusted mean difference -0·9; 95% confidence interval -1·5 to -0·3; P = 0·004) of positive emboli at day seven. CONCLUSIONS: Dual treatment with clopidogrel and aspirin for seven-days is more effective than aspirin alone to reduce microembolic signals in patients with intracranial arterial stenosis.

Suggestion AGAINST warfarin after 3 months post maze procedure

The impact of CHADS(2) score on late stroke after the Cox maze procedure; Pet M, Robertson JO, Bailey M, Guthrie TJ, Moon MR, Lawton JS, Rinne A, Damiano RJ, Maniar HS; Journal of Thoracic and Cardiovascular Surgery (Jul 2012)

OBJECTIVE: The Heart Rhythm Society, European Heart Rhythm Association, and European Cardiac Arrhythmia Society jointly recommend indefinite warfarin anticoagulation in patients with CHADS(2) (congestive heart failure, hypertension, age, diabetes, and stroke) score of at least 2 who have undergone ablation for atrial fibrillation. This study determined the impact of CHADS(2) score on risk of late stroke or transient ischemic attack after the performance of a surgical Cox maze procedure. METHODS: A retrospective review of 433 patients who underwent a Cox maze procedure at our institution was conducted. Three months after surgery, warfarin was discontinued regardless of CHADS(2) score if the patient showed no evidence of atrial fibrillation, was off antiarrhythmic medications, and had no other indication for anticoagulation. A follow-up questionnaire was used to determine whether any neurologic event had occurred since surgery. RESULTS: Follow-up was obtained for 90% of the study group (389/433) at a mean of 6.6 ± 5.0 years. Among these patients, 32% (125/389) had a CHADS(2) score of at least 2, of whom only 40% (51/125) remained on long-term warfarin after surgery. Six patients had late neurologic events (annualized risk of 0.2%). Neither CHADS(2) score nor warfarin anticoagulation was significantly associated with the occurrence of late neurologic events. Among the individual CHADS(2) criteria, both diabetes mellitus and previous stroke or transient ischemic attack were predictive of late neurologic events. CONCLUSIONS: The risk of stroke or transient ischemic attack in patients after a surgical Cox maze procedure was low and not associated with CHADS(2) score or warfarin use. Given the known risks of warfarin, we recommend discontinuation of anticoagulation 3 months after the procedure if the patient has no evidence of atrial fibrillation, has discontinued antiarrhythmic medications, and is without any other indication for systemic anticoagulation.

19

asa + plavix decreased MI's, increases fatal hemorrhages, no effect on mortality

Effect of addition of clopidogrel to aspirin on mortality: systematic review of randomized trials; Palacio S, Hart RG, Pearce LA, Benavente OR; Stroke 43 (8), 2157-62 (Aug 2012)

 

BACKGROUND AND PURPOSE In the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, addition of clopidogrel to aspirin was associated with an unexpected increase in mortality in patients with lacunar strokes. We assessed the effect of the addition of clopidogrel to aspirin on mortality in a meta-analysis of published randomized trials. METHODSRandomized trials in which clopidogrel was added to aspirin in subjects with vascular disease or vascular risk factors were identified. Trials were restricted to those with a mean follow-up of ≥14 days in which both the combination of aspirin and clopidogrel was tested and mortality was reported. RESULTSTwelve trials included 90 934 participants (mean age, 63 years; 70% men; median follow-up, 1 year) with 6849 observed deaths. There was no significant increase in mortality with the combination therapy either in 4 short-term (14 days-3 months; OR, 0.93; 95% CI, 0.87-0.99) or in 7 long-term (>3 months; hazard ratio, 0.97; 95% CI, 0.91-1.04) trials after 1 long-term trial (the SPS3 trial) was excluded because of heterogeneity. Addition of clopidogrel was associated with an increase in fatal hemorrhage (OR, 1.35; 95% CI, 0.97-1.90) and a reduction in myocardial infarction (OR, 0.82; 95% CI, 0.74-0.91). CONCLUSIONSThe addition of clopidogrel to aspirin has no overall effect on mortality. The SPS3 trial results are outliers, possibly because of a lower prevalence of coronary artery ischemia. Addition of clopidogrel to aspirin increases fatal bleeding and reduces myocardial infarction. Clinical Trial Registration- URL: http//www.clinicaltrials.gov. Unique identifier: NCT00059306.

 

Comment -- metaanalysis improves our knowledge over SPS3 results which are outliers